Conventionally, various diseases have been treated and prevented by using a “single target-single disease” approach to control a specific hormone or to target a single receptor. However, such an approach has not been sufficient to treat and prevent many diseases and may cause unexpected side effects.
For example, according to a current mechanism of action of antidepressants, symptoms of depression are reduced or relieved by increasing the amount of 5-HT as a neurotransmitter in a human body, and such an antidepressant has many serious side effects such as an increase in suicide rate, headache, diarrhea, melosalgia, a skin rash, palpitations, repetitive spasms, hyperhidrosis, edema, hypoactive sexual desire disorders, erectile dysfunction, and the like. Further, corticosteroids have been used to treat atopic dermatitis, but when discontinuing such a treatment, there may be a risk of rebound effects (dramatic worsening in a diseased part after discontinuing a medication). Therefore, nonsteroidal anti-inflammatory drugs or antihistamines that do not contain hormones such as corticosteroids have been used. However, such drugs have weak efficacy, and, thus, it is difficult to completely treat the diseases.
In order to solve these problems, as a suggestion for another direction of drug development, various studies into multi-target drugs have been carried out. However, at present, only combination drugs including two or three drugs have been used mostly for anticancer treatments, but there is limited knowledge about how to combine various targets.
Meanwhile, recently, in order to treat or prevent diseases, functional foods have been researched and produced in various forms such as functional foods or functional beverages with the purposes of vitality promotion, obesity prevention, improvement in atopic dermatitis, skin health, scalp health, pain control, refreshment, and the like. In addition to such functional foods, cosmetic compositions have been continuously researched and developed to achieve an aesthetic purpose, a therapeutic purpose, and a preventive purpose in the fields of skin whitening, antiwrinkle, skin elasticity, hair, and scalp. However, in most cases, by formulating various kinds of chemical components, efficacy corresponding to such components is given to cosmetics, or various kinds of formulations are created by creatively processing basic components. However, such formulations as described above also need a cosmetic composition having more various and higher efficacy and a toxicity problem still needs to be solved for safety in skin.
In view of the foregoing, recently, a lot of studies into natural substances having efficacy against diseases have been actively carried out. For example, Nelumbinis Semen extract has been used to treat depression; a method of producing seanol-based cream for pain treatment and anti-inflammation is known; salt, Phyllostachys nigra Munro extract, and the like have been provided to prevent and treat skin inflammations (Korean Patent Application Laid-open No. 10-2009-0113462); Reynoutria elliptica extract, Sanguisorba officinalis L. extract, Coptis chinensis extract, and the like have been provided to improve atopic dermatitis (Korean Patent Application Laid-open No. 10-2007-0079497); and a combination of Glycyrrhiza uralensis Fischer, green tea, Asiasari radix extract, and chitosan has been suggested to prevent periodontal diseases. Such natural substances can solve a toxicity problem of conventional compound-containing compositions and can be easily applied to functional foods, cosmetics, medicines, and the like. Therefore, natural substances have been recently applied to medicines, cosmetics, and functional foods in various ways.
Conventionally, however, it is general to produce a functional food composition based on descriptions of old documents or experience or to produce a composition based on a known-mechanism and apply the composition to a clinical test. There has not been a research study like the present invention on a specific combination of natural substances or compounds inducing synergistic effects based on a specific receptor-related mechanism.
Meanwhile, pain is a kind of warning system telling us that something is wrong in our body, and it is an essential symptom to maintain our normal life and can be typically classified into acute pain and chronic pain.
Although a lot of neuropathologic studies on pain have been actively carried out and various studies into treatments for pain have been carried out, even now, most treatments for pain depend on narcotic analgesics developed in the past.
A nervous system in charge of pain has a very complicated and parallel structure. A selective and potent drug on a single target may have lower efficacy than expected and is more likely to cause serious side effects. Therefore, there is a need for development of a multi-target drug capable of simultaneously controlling a pain signal process, or a central sensitization mechanism by adjusting multiple targets.
Pain relievers developed so far act on peripheral nerves or central nerves and relieve pain and can be typically classified into a nonsteroidal anti-inflammatory drug (NSAID), a COX-2 inhibitor, an opiate, a morphinomimetic, and flupirtine. It is reported that these pain relievers have many side effects and an addiction problem.
Accordingly, there is a significant need to develop novel medicaments capable of solving different side effects and the addiction problem of conventional pain relievers as well as relieving symptoms specific to pains.
Although a molecular-biological mechanism of pain and functions of drug targets based on the above mechanism have been relatively clearly disclosed, there is still considerable lack of understanding about a mechanism which results in pruritus (itching). However, since a significantly similar aspect is expressed between mechanisms respectively, in charge of pain and itching in peripheral tissues and spinal cords, the established mechanism and treatments for pain have also been applied to itching.
There is a complicated interaction between pain and itching. Usually, we strongly scratch an itchy spot to remove itching and this nociceptive stimulus suppresses itching, or an opioid analgesic causes itching. Such an antagonistic interaction is known. In addition, it has been discovered that the mechanisms in charge of pain and itching (central/peripheral sensitization, sense of difference, hypersensitization, etc.) significantly coincides with neuromodulators (NGF (nerve growth factor), TRPV1 (transient receptor potential vanilloid receptor 1), PARs (protease-activated receptors), etc.) as mediators thereof, which has been applied to treatments. By using a close relationship between peripheral mechanisms of two senses, a medicine, such as anti-NGF, having analgesic efficacy and anti-inflammatory efficacy has been developed, and gabapentin wieldy used as a medicine for neuropathic pain has been successfully applied to a medicine for chronic itching.
Causes of atopic dermatitis are not clear, and it has been reported that genetic factors, environmental factors, and immunologic factors are involved in atopic dermatitis. Currently-used medicines for atopic dermatitis mainly relieve symptoms, and, thus, there is an urgent requirement to develop a fundamental and innovative medicine. Atopic dermatitis occurs with a cycle of itching-scratching-further itching in which if one cannot treat or endure early itching and scratching an itchy spot, itching is worsened. As a result, in addition to pruritus (localized or systemic itching), other symptoms, such as rashes, chronic relapses, etc., of atopic dermatitis occur. Therefore, atopic dermatitis can be treated fundamentally by developing a drug capable of suppressing and treating early itching and preventing skin damage or an inflammatory response after scratches.
Based on such studies, the present inventors have made all possible efforts to supply a composite composition whose efficacy can be amplified by synergistic effects between components even if a small amount of the composite composition is used and a pharmaceutical composition having antipruritic efficacy and atopic dermatitis treatment efficacy as well as analgesic efficacy obtained by synergistic effects between drugs by using a multi-targeting mechanism. As a result, the present inventors have found that when substances acting on three targets with established synergistic effects are combined (particularly, natural substances functioning as agonists or antagonists of such receptors are appropriately combined), synergistic effects of multi-targeting bring about an increase in efficacy including pain control, relief of skin diseases such as pruritus and atopic dermatitis, prevention or improvement of depression, refreshment, wrinkle improvement, skin whitening, prevention or improvement of athlete's foot, hair growth promotion, etc. and completed the present invention.
The information as described in the above background art is only provided to improve understanding of a background technology of the present invention, however, other information with respect to prior art well known to persons having ordinary skill in the art to which the present invention pertains, may not be included therein.